Abnormal transmission to receptors in the central nervous system (CNS) have been implicated in a wide variety of diseases, such as Parkinson's disease, psychosis, and many others. Currently, many therapies for these diseases are based upon the use of a medicament as an agonist to stimulate a receptor, or as an antagonist to block a receptor. For example, the treatment of psychosis has been associated with medicament antagonism with dopaminergic receptors.
The ability of a medicament to be effective in vivo to effectively interact with CNS receptors depends upon many factors, including the binding affinity of the medicament for a receptor, the medicaments ability to cross the blood-brain barrier, and the selectivity of the medicament for a targeted receptor. For example, to treat psychotic activity a medicament would be a selective antagonist for the D4 dopamine receptor.
To date, many medicaments with good binding affinities for a particular CNS receptor also bind to non-targeted receptors, often resulting in undesirable side-effects. For example, common side-effects of anti-psychotic drugs include extrapyramidal side-effects. Similarly, some atypical anti-psychotic drugs, such as clozapine which is selective for the D4 receptor, have not exhibited extrapyramidal side-effects but have had severe effects upon the patient's white blood cells, such as agranulocytosis.
Consequently, compositions are needed that can cross the blood-brain barrier to act in vivo and selectively target a CNS receptor without causing severe extrapyramidal side-effects, agranulocytosis or other side-effects associated with current medicaments.